Ras oncogenes are part of a large family of related proteins. Many of these Ras-related proteins are suspected of playing a role in tumorigenic transformation. Indeed, certain Ras related proteins appear to serve as downstream components of Ras signaling and transformsation. We have focussed on those proteins which not only share structural homology to Ras, but also undergo the same type of lipid processing as Ras, farnesylation. Drugs directed at inhibiting farnesylation (Farnesyl transferase inhibitors or FTIs), which is essentail for Ras function, are currently in clinical trials at the NIH. Consequently, understanding the overall importance of other farnesylated proteins in growth and development may have considerable clinical relevance. We have found that the novel Ras-related proteins Rho6 and Rho7 are also farnesylated and appear to act as inhibitors of certain aspects of Ras transformation. Moreover, the inhibition is dependent upon Rho6/7 farnesylation. Studies are underway to determine if these proteins may play a role as tumor suppressors. If so, the long term use of FTIs may serve to inadvertantly inactivate tumor suppresors. We are also examining a novel Ras related protein identified by data base searching which we have designated ARHI2. This protein shares homology with Ras and with the tumor suppresor Noey1/Arhi.